Based on a systematic literature search using the terms “mesonephric-like adenocarcinoma” and “ovary” in the PubMed, Wanfang, and CNKI databases, 19 mesonephric-like adenocarcinoma of the ovary cases were reported, as shown in Table 1.

Mesonephric-like adenocarcinoma and mesonephric-duct adenocarcinoma are rare malignancies of the female reproductive system. Current studies suggest that mesonephric-duct adenocarcinoma is of mesonephric origin, often occurring in the cervix and vagina, and is associated with mesonephric ductal remnants and mesonephric ductal hyperplasia. Mesonephric ductal remnants may be seen around the tumor tissue. Mesonephric-like adenocarcinoma, a new class of rare subtypes included in the WHO (2020) Classification of Tumors of the Female Reproductive System, does not have mesonephric ductal remnants around the tumor tissue but has histologic, immunohistochemical, and molecular features similar to those of mesonephric-duct adenocarcinoma [1]. The histologic origin of mesonephric-like adenocarcinoma has been controversial. It has been suggested that it may originate from the epithelium of the Müllerian duct and then differentiate along the mesonephric pathway [2]. Among the 39 cases of ovarian mesonephric-like adenocarcinoma statistically analyzed by Deolet E [3] et al., 16 were associated with the epithelium of the Müllerian duct. Yano et al., Dundr et al., McCluggage et al., and Chapel et al. found that mesonephric-like adenocarcinomas and endometrial carcinomas, plasmacytoid junctional tumors, and low-grade plasmacytoid carcinomas of the ovary share common mutations in the KRAS and NRAS genes, which also supports the idea that mesonephric-like adenocarcinoma (MLA) is of the Mullerian origin [4,5,6,7]. In this case, the patient had a history of endometriosis (EMS), and the coexistence of ovarian-like adenocarcinoma and mature cystic teratoma of the ovary in this pathologic tissue suggested that the mesonephric-like adenocarcinoma in the ovary may originate in the Mullerian duct.

Mesonephric-like adenocarcinoma (MLA) of the ovary is extremely rare clinically, and there are few related reports at home and abroad. Its clinical manifestations are not significantly different from other types of ovarian cancers, often asymptomatic in the early stage, and chronic pelvic pain and abnormal uterine bleeding, postmenopausal irregular bleeding, abdominal distention, or asymptomatic in the late stage. The confirmation of diagnosis depends on pathological and immunohistochemical methods [8]. Histologically, mesonephric-like adenocarcinoma may show different patterns, such as reticular, papillary, tubular, gonadal, glandular, glomeruloid, fusiform, and sieve-like, and the same tumor often has a mixture of two or more growth modalities. Eosinophilic colloid-like material is commonly found in the lumen of the tubules [9,10,11]. Cytologically, tumor cells are flat, cuboidal, and columnar, mildly to moderately heterogeneous, while highly heterogeneous is uncommon. The cytoplasm is eosinophilic; nuclei are flat or ovoid, with vesicular nuclei, nuclear grooves, and nuclear overlap visible, without squamous, ciliated, and mucinous chemotaxis, and there is no mesonephric remnant in the periphery [12]. Immunohistochemistry is important for its diagnosis. Mesonephric-like adenocarcinoma is often positive for calretinin, GATA-3, CD10, and TTF-1, sometimes positive for P53, and negative for ER and PR. PR is a more reliable negative marker compared with ER [13]. Studies have shown that GATA3 and/or thyroid transcription factor 1 (TTF1) are considered as its markers [3]. Molecularly, G12V, and G12D are the most common KRAS mutations in mesonephric-like adenocarcinoma, and concurrent ARID1A and PIK3CA mutations are relatively common, with 1q copy number gain being the most common [2, 4, 14, 15]. Some of them also had a 1p loss. p53 expression adopts a wild-type pattern, p16 is patchy and WT1 is negative. However, no PTEN mutations/deletions were observed, microsatellite was unstable, which is different from the mesonephric-duct adenocarcinoma [16,17,18]. Studies have shown that the combined testing of CA125, CA199, and CEA in patients with ovarian malignant tumors can improve the accuracy of early diagnosis of ovarian cancer. In this case, the patient demonstrated preoperative elevation of CA125 and CA199 and postoperative declines, which can help predict the disease progression and prognosis evaluation [19,20,21].

Studies have shown that mesonephric-like adenocarcinoma is highly invasive and can recur and metastasize at an early stage. 39% of patients with mesonephric-like adenocarcinoma of the ovary were at stages II-IV at the time of diagnosis, and 43% of patients had lymphatic metastases. Tumors are more likely to metastasize when they have a diameter of > 4 cm, unclear tumor boundary, relatively high clinical stage (III-IV), large areas of necrosis, high nuclear fission index (> 10/10HPF), and lymphovascular invasion [12]. There is currently no uniformly recommended surgical method, and the general approach is total hysterectomy with bilateral adnexectomy, omentectomy, and pelvic lymphadenectomy. After surgery, chemotherapy, radiotherapy, or combined radiotherapy is used. Paclitaxel combined with carboplatin is generally recommended as the first-line chemotherapy regimen [22]. Inhibition of the RAS/MAPK pathway can also be a therapeutic modality when the mesonephric-like adenocarcinoma is combined with KRAS/NRAS mutations [23]. After standard treatment, 42% of patients may still experience a recurrence, and the most common sites of recurrence are the lung, omentum majus, liver, ossa pubis, perihepatic, mesentery, and peritoneum regions [22].